Research Focus

Hematopoietic stem cells (HSCs) reside in the bone marrow and are defined by their capacity for lifetime maintenance of the blood and bone marrow, achieved through their differentiation into the myriad of cellular components, as well as their ability to generate additional stem cells via self-renewal. The mechanisms that instruct the fate of stem cells toward differentiation versus self-renewal are still relatively poorly understood. A number of transcription factors have been identified as critical for HSC maintenance and self-renewal; however, we have little insight into how these factors are orchestrated by epigenetic mechanisms to ensure blood homeostasis. The central theme of my research is understanding how epigenetic marks such as histone methylation and acetylation, DNA methylation, and 5-hydroxymethylation co-ordinately act to regulate normal HSC function and how these processes go awry in hematopoietic diseases such as leukemia and lymphoma. We also use various mouse genetic models to study the roles of genetic mutations of different components of the epigenetic machinery in cancers of the blood and bone marrow. 

YouTube Video

In the NEWs

 Congratulations to Cates Mallaney for receiving an NIH F31 fellowship to fund her work on investigating the role of histone demethylase KDM6B in hematopoiesis. The award provides funding from July 2016-2019. 

Congratulations to our very own Hamza Celik on receiving the ASH Scholar Award! Hamza has 
received this award in his second year as post-doctoral researcher in the lab. He will be honored along with the other recipients at the 58th annual ASH conference in December of 2016. Check out Washington Universities Newsletter on Dr. Celik and the other two ASH award recipients from Washington University at the link below.

Recent Publications 

Dnmt3a regulates T-cell development and suppresses T-ALL transformation
AC Kramer, A Kothari, WC Wilson, H Celik, J Nikitas, C Mallaney, EL Ostrander, E Eultgen, A Martens, MC Valentine, AL Young, TE Druley, ME Figueroa, B Zhang and GA Challen
Leukemia (2017) 1-12

Reprogrammable CRISPR/Cas9-based system for inducing site-specific DNA methylation
McDonald JI*, Celik H*, Rois LE, Fishberger G, Fowler T, Rees R, Kramer A, Martens A, Edwards JR, Challen GA. 
Biology Open [ In press - Accepted April 19, 2016]
DNA methylation in normal and malignant hematopoiesis. 
Celik H, Kramer A, Challen GA.
Int J Hematol, 2016 Mar 4, [Epub ahead of print]